Antiplatelet and antithrombotic effects of cordycepin-enriched WIB-801CE from Cordyceps militaris ex vivo, in vivo, and in vitro

Autor: Hyuk-Woo Kwon, Woo Jeong Ok, Jong-Lae Kim, Jung-Hae Shin, Min Ji Kim, Jun-Hee Noh, Hwa-Jin Park, Deok Hwi Lim, Hyun-Hong Kim, Gi Suk Nam, Ho-Kyun Kwon, Je-Young Lee
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Serotonin
Platelet Aggregation
Thromboxane A2 synthase
Drug Evaluation
Preclinical
Clot retraction
030204 cardiovascular system & hematology
Pharmacology
Nitric Oxide
ERK2
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Thromboxane A2
0302 clinical medicine
Cordycepin
Fibrinolytic Agents
In vivo
Medicine
Animals
Platelet
Platelet activation
Phosphorylation
Blood Coagulation
Mice
Inbred ICR
Arachidonic Acid
business.industry
Plant Extracts
WIB-801CE
Platelet aggregation
TXA(2)
Thromboxane A(2) synthase
Arachidonic acid release
p(38 MAPK)
Thrombus
TXA2
General Medicine
030104 developmental biology
Complementary and alternative medicine
chemistry
Type C Phospholipases
Cordyceps
p38MAPK
Platelet aggregation inhibitor
Calcium
business
Ex vivo
Platelet Aggregation Inhibitors
Research Article
Zdroj: BMC Complementary and Alternative Medicine
BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE(16)
ISSN: 1472-6882
Popis: Background A species of the fungal genus Cordyceps has been used as a complementary and alternative medicine of traditional Chinese medicine, and its major component cordycepin and cordycepin-enriched WIB-801CE are known to have antiplatelet effects in vitro. However, it is unknown whether they have also endogenous antiplatelet and antithrombotic effects. In this study, to resolve these doubts, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from Cordyceps militaris-hypha, then evaluated its ex vivo, in vivo, and in vitro antiplatelet and antithrombotic effects. Methods Ex vivo effects of WIB-801CE on collagen- and ADP-induced platelet aggregation, serotonin release, thromboxane A2 (TXA2) production and its associated activities of enzymes [cyclooxygenase-1 (COX-1), TXA2 synthase (TXAS)], arachidonic acid (AA) release and its associated phosphorylation of phospholipase Cβ3, phospholipase Cγ2 or cytosolic phospholipase A2, mitogen-activated protein kinase (MAPK) [p38 MAPK, extracellular signal-regulated kinase (ERK)], and blood coagulation time in rats were investigated. In vivo effects of WIB-801CE on collagen plus epinephrine-induced acute pulmonary thromboembolism, and tail bleeding time in mice were also inquired. In vitro effects of WIB-801CE on cytotoxicity, and fibrin clot retraction in human platelets, and nitric oxide (NO) production in RAW264.7 cells or free radical scavenging activity were studied. Results Cordycepin-enriched WIB-801CE inhibited ex vivo platelet aggregation, TXA2 production, AA release, TXAS activity, serotonin release, and p38 MAPK and ERK2 phosphorylation in collagen- and ADP-activated rat platelets without affecting blood coagulation. Furthermore, WIB-801CE manifested in vivo inhibitory effect on collagen plus epinephrine-induced pulmonary thromboembolism mice model. WIB-801CE inhibited in vitro NO production and fibrin clot retraction, but elevated free radical scavenging activity without affecting cytotoxicity against human platelets. Conclusion WIB-801CE inhibited collagen- and ADP-induced platelet activation and its associated thrombus formation ex vivo and in vivo. These were resulted from down-regulation of TXA2 production and its related AA release and TXAS activity, and p38 MAPK and ERK2 activation. These results suggest that WIB-801CE has therapeutic potential to treat platelet activation-mediated thrombotic diseases in vivo.
Databáze: OpenAIRE
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